Evaluation of a panel of furochromenones as the activator and inhibitor of tyrosinase.

Tyrosinase is a copper-containing enzyme involved in the biosynthesis of melanin pigment. While the excess production of melanin causes hyperpigmentation of human skin, hypopigmentation results in medical conditions like vitiligo. Tyrosinase inhibitors could be used as efficient skin whitening agents and tyrosinase agonists could be used for enhanced melanin synthesis and skin protection from UV exposure. Among a wide range of tyrosinase-regulating compounds, natural and synthetic derivatives of furochromenones, such as 8-methoxypsoralen (8-MOP), are known to both activate and inhibit tyrosinase. We recently reported a synthetic approach to generate a variety of dihydrofuro[3,2-c]chromenones and furo[3,2-c]chromenones in a metal-free condition. In the present study, we investigated these compounds for their potential as antagonists or agonists of tyrosinase. Using fungal tyrosinase-based in vitro biochemical assay, we obtained one compound (3k) which could inhibit tyrosinase activity, and the other compound (4f) that stimulated tyrosinase activity. The kinetic studies revealed that compound 3k caused 'mixed' type tyrosinase inhibition and 4f stimulated the catalytic efficiency. Studying the mechanisms of these compounds may provide a basis for the development of new effective tyrosinase inhibitors or activators.

Solvent controlled synthesis of 2,3-diarylepoxy indenones and α-hydroxy diarylindanones and their evaluation as inhibitors of DNA alkylation repair.

Herein, we report a novel and unexpected metal-free oxygenation of 2,3-diphenyl-1-indenones, under an oxygen atmosphere (air), to either 2,3-epoxy-2,3-diphenyl-1-indenone or 2-hydroxy-2,3-diphenyl-1-indanone, depending on the conditions. Several bioactive epoxy indenones and one-pot α-hydroxy indanones (α-acyloin) were synthesized from 2,3-diaryl dihydroindanone and 2,3-diarylindenone, respectively. A plausible reaction mechanism is also proposed, where oxygenation would take place at the α-position and further proton abstraction from the ß-position leads to epoxy indenone derivatives. A one-pot cis-hydroxy indanone protocol is also achieved directly from biaryl indenone via reduction, epimerization, and oxygenation. The synthesized compounds were evaluated for inhibitory activity against the DNA repair protein AlkB. Among the screened (17 tested) compounds, one epoxide derivative was found to be a specific inhibitor of AlkB enzyme function.

Synthesis and antibacterial activities of marine natural product ianthelliformisamines and subereamine synthetic analogues.

Marine sponges of the genusSuberea produce variety of brominated tyrosine alkaloids which display diverse range of biological activities including antiproliferative, antimicrobial and antimalarial activities. In continuation of our search for biologically active marine natural products for antibacterial compounds, we report here the synthesis and evaluation of biological activity of panel of ianthelliformisamines and subereamine analogues using the literature known acid-amine coupling reaction. Several derivatives of Ianthelliformisamine were achieved by the coupling of Boc-protected polyamine chain with brominated aromatic acrylic acid derivatives by varying the bromine substituents on aromatic acid derivatives, amine spacer as well as geometry of the double bond, and then Boc-deprotection using TFA. Similarly, subereamine analogues were also synthesized employing coupling reaction between various brominated phenyl acrylic acids with commercially available chiral amino ester derivatives followed by ester hydrolysis. We screened these synthetic analogues for antibacterial activity against both Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) strains. One of the compound 7c showed bactericidal activity against Staphylococcus aureus with an IC50 value of 3.8 µM (MIC = 25 µM).